Trypanosomes infect a variety of hosts and cause various diseases, including the fatal human diseases sleeping sickness, caused by Trypanosoma brucei, and Chagas disease, caused by Trypanosoma cruzi. The parasites use glycosomes—organelles similar to peroxisomes to compartmentalize glucose metabolism. Proteins PEX14 and PEX5 are essential parts of the glycosomal import machinery. They bind each other by direct protein-protein interface. It has been shown that in the absence of PEX14 glucose is toxic to the parasite (Furuya, et al., PNAS 99 (2002), 14177-14182).
Current treatment of trypanosomiasis is complex and can trigger dangerous, adverse reactions. This makes practical treatment difficult in developing countries. E.g. approximately 70 million people are living in endangered areas with regard to African sleeping sickness. Despite treatment efforts, the estimated number of cases in 2009 exceeded 30 000 (Source: WHO fact sheet No 259). In addition, the parasite causes approximately 3 million deaths in cattle per year, amounting to an estimated loss of 4.75 billion dollars per year. The main currently used trypanolytic drugs in human medicine are pentamidine, suramin, melarsoprol and eflornithine. All these compounds are abundant in undesirable side effects and require strict and difficult application regimen (WHO fact sheet No 259). Regarding the therapy in the veterinary field, there are three trypanolytic drugs available—isometamidium chloride, diminazene aceturate and homidium (bromide and chloride). One risk of using existing trypanolytic drugs is the development and spread of drug resistance in parasite populations. Resistance to one or more of the trypanolytic drugs used in cattle has been reported in at least 13 countries of sub-Saharan Africa (Source: webpage of the Food And Agriculture Organization of the United Nations).
Thus, there is still a need to identify alternative, improved and/or integrated means or methods that address one or more problems, including those described above such as in the treatment (including prophylactic treatment) of one or more conditions, disorders or diseases (or related conditions or symptoms) caused or mediated by a parasite of the family Trypanosomatidae and/or agents and pharmaceutical compositions useful for such treatment. Such an object underlying the present invention is solved by the subject-matter as disclosed or defined anywhere herein, for example by the subject-matter of the attached claims.